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Chiarelli M, De Simone M, Cioffi G, Cioffi U. New paradigm of oral rehydration in patients affected by irritable bowel syndrome with chronic diarrhea. World J Gastrointest Pharmacol Ther 2024; 15:90933. [PMID: 38590832 PMCID: PMC10999031 DOI: 10.4292/wjgpt.v15.i1.90933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/20/2024] [Accepted: 02/28/2024] [Indexed: 03/18/2024] Open
Abstract
Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms. This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool. International surveys about this disease report a global prevalence of about 1.5%. A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea. It is composed of water, electrolytes, and five selected amino acids that function as sodium co-transporters without containing glucose. In recent years, some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis, reporting good results. Recently, a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome. The research was based on a real-life methodology minimizing the disruption of the routine care. One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk. Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction. Based on this data, we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea. It is certainly necessary to plan high-quality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea. Probably in the near future all oral rehydration solutions will contain amino acids.
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Affiliation(s)
- Marco Chiarelli
- Department of Emergency and Robotic Surgery, A. Manzoni Hospital–ASST Lecco, Lecco 23900, Italy
| | - Matilde De Simone
- Department of Surgery, University of Milan, Via F. Sforza 35, 20122 Milano, Milano 20122, Italy
| | - Gerardo Cioffi
- Department of Sciences and Technologies, Unisannio, Benevento 82100, Italy
| | - Ugo Cioffi
- Department of Surgery, University of Milan, Milano 20122, Italy
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Niles SE, Blazy P, Cheuvront SN, Kenefick RW, Vidyasagar S, Smith AB, Fawkes N, Denman W. Effectiveness of an amino acid beverage formulation in diarrhea-predominant irritable bowel syndrome: A pragmatic real-world study. World J Gastrointest Pharmacol Ther 2023; 14:39-49. [PMID: 38174291 PMCID: PMC10758599 DOI: 10.4292/wjgpt.v14.i5.39] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 10/16/2023] [Accepted: 11/15/2023] [Indexed: 12/12/2023] Open
Abstract
BACKGROUND Amino-acid based medical foods have shown promise in alleviating symptoms of drug induced gastrointestinal side effects; particularly, diarrhea-predominant symptoms. Irritable bowel syndrome (IBS) is a gastrointestinal disorder that affects up to 9% of people globally, with diarrhea predominant IBS (IBS-D) being the most prevalent subtype. Further trials are needed to explore potential added benefits when integrated into standard care for IBS-D. AIM To assess the effectiveness of an amino acid-based medical food as an adjunct to standard of care for adults with IBS-D. METHODS This is a pragmatic, real world, open label, single arm study comparing a 2-week baseline assessment to a 2-week intervention period. One hundred adults, aged 18 to 65 years, with IBS-D, according to Rome IV criteria, were enrolled after completing a 2-week baseline assessment period and received a 2-week supply of an amino acid based medical food which was consumed at home twice daily on top of their standard of care. The primary outcome was an assessment of tolerability after 2-weeks of consumption, while secondary outcomes included changes in stool consistency (Bristol Stool Form Scale), severity of abdominal pain & discomfort, symptoms of urgency, Global Improvement Survey (GIS), and the IBS severity scoring system (IBS-SSS). RESULTS The test product was well-tolerated as each participant successfully completed the full 14-day trial, and there were no instances of dropouts or discontinuation of the study product reported. Forty percent of participants achieved a 50% or more reduction in the number of days with type 6-7 bowel movements (IBS-D stool consistency responders). Fifty-three percent of participants achieved a clinically meaningful reduction of 30% in mean weekly pain scores, and 55% experienced the same for mean weekly discomfort scores (IBS-D pain and discomfort responders). Participants experienced a mean -109.4 (95% confidence interval: -130.1, -88.8) point reduction on the IBS-SSS and 52% experienced a minimally clinically important difference of > 95 points. An IBS-SSS category shift from severe to moderate or mild occurred in 69% of participants. For functional symptoms, 76% of participants reported symptom relief on the GIS. CONCLUSION The amino acid-based medical food was well-tolerated, when added to the standard of care, and demonstrated improvements in both overall IBS symptom severity and IBS-D symptoms within just 2 wk.
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Affiliation(s)
- Samantha E Niles
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Phil Blazy
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Samuel N Cheuvront
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Robert W Kenefick
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Sadasivan Vidyasagar
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
- Department of Radiation Oncology, University of Florida, Gainesville, FL 32611, United States
| | - Adam B Smith
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - Neil Fawkes
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
| | - William Denman
- Department of Research and Development, Entrinsic Bioscience, Norwood, MA 02062, United States
- Department of Anesthesiology, Massachusetts General Hospital, Boston, MA 02114, United States
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Lahiri KR, Singh R, Apte M, Patil M, Taksande A, Varona R, Chatterjee G, Verma M, Brette S, Perez MIII. Efficacy and safety of Bacillus clausii (O/C, N/R, SIN, T) probiotic combined with oral rehydration therapy (ORT) and zinc in acute diarrhea in children: a randomized, double-blind, placebo-controlled study in India. Trop Dis Travel Med Vaccines 2022; 8:9. [PMID: 35397572 PMCID: PMC8994895 DOI: 10.1186/s40794-022-00166-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 01/13/2022] [Indexed: 11/20/2022] Open
Abstract
Background Childhood diarrhea remains a major disease burden, particularly in developing countries, and is a leading cause of death in children aged < 5 years, worldwide. Treatment of acute diarrhea now includes probiotics to potentially reduce the duration and severity of the illness. This phase 3, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of four strains (O/C, N/R, SIN, T) of Bacillus clausii probiotic (Enterogermina®) plus oral rehydration therapy (ORT) and zinc, versus placebo plus ORT and zinc, in infants and children in India with acute moderate diarrhea. Methods Patients aged 6 months to 5 years with acute moderate diarrhea (WHO 2005 definition) of < 48 h’ duration were randomly assigned to receive one mini bottle of either polyantibiotic-resistant B. clausii (oral suspension of 2 billion spores per 5 mL bottle) or matching placebo twice daily (morning and evening) for 5 days. Exclusion criteria included known hypersensitivity to B. clausii or excipients in the study treatment, or to other probiotics. Patients were admitted to hospital from Day 1 and discharged ≥6 h after diarrhea resolution, or a maximum of 5 days. The primary endpoint was duration of acute diarrhea from randomization to recovery. Secondary endpoints included frequency of stools, diapers with stools, or dehydration status. Results In total, 457 patients were randomized; 454 were treated. Similar proportions of patients showed recovery from diarrhea over the 120 h after randomization (97.0% in the B. clausii group [n = 227]; 98.0% on placebo [n = 227]). Median time to recovery was also similar: 42.83 (95% CI: 40.90–44.90) hours for B. clausii and 42.13 (95% CI: 39.80–43.87) hours for placebo. However, no statistically significant difference was observed between groups (hazard ratio = 0.93 [95% CI: 0.77–1.13]; p = 0.6968); nor were there statistically significant differences between groups for the secondary endpoints. Treatment with B. clausii was well tolerated with incidence of adverse events (9.7%) similar to that for placebo (12.3%). Conclusions No significant difference in efficacy between B. clausii and placebo was demonstrated. Sample size may have been inadequate to allow detection of a between-group difference in efficacy, given the mild/moderate severity (only ~ 20% of patients had nausea/vomiting or abdominal pains) and short duration of disease among subjects, the relatively late start of treatment (most were already on Day 2 of their disease episode when study treatment started) and the effectiveness of the standard of care with ORT and zinc in both treatment groups. Trial registration CTRI number CTRI/2018/10/016053. Registered on 17 October 2018. EudraCT number 2016-005165-31. Registered 14 May 2020 (retrospectively registered). Supplementary Information The online version contains supplementary material available at 10.1186/s40794-022-00166-6.
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Cheuvront SN, Kenefick RW, Luque L, Mitchell KM, Vidyasagar S. Are oral rehydration solutions optimized for treating diarrhea? Nutr Health 2021; 27:461-465. [PMID: 33583247 DOI: 10.1177/0260106021991641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND A historical turning point occurred in the treatment of diarrhea when it was discovered that glucose could enhance intestinal sodium and water absorption. Adding glucose to salt water (oral rehydration solution, ORS) more efficiently replaced intestinal water and salt losses. AIM Provide a novel hypothesis to explain why mainstream use of ORS has been strongly recommended, but weakly adopted. METHODS Traditional (absorptive) and novel (secretory) physiological functions of glucose in an ORS were reviewed. RESULTS Small amounts of glucose can stimulate both intestinal absorption and secretion. Glucose can exacerbate a net secretory state and may aggravate pathogen-induced diarrhea, particularly for pathogens that affect glucose transport. CONCLUSION A hypothesis is made to explain why glucose-based ORS does not appreciably reduce diarrheal stool volume and why modern food science initiatives should focus on ORS formulations that replace water and electrolytes while also reducing stool volume and duration of diarrhea.
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Affiliation(s)
- Henry J Binder
- Section of Digestive Diseases, Department of Internal Medicine, Yale University, PO Box 208019, New Haven, CT, 06520, USA.
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Na +-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na + Recycling in Mouse Small Intestine. Int J Mol Sci 2020; 21:ijms21020376. [PMID: 31936130 PMCID: PMC7013606 DOI: 10.3390/ijms21020376] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 12/27/2019] [Accepted: 12/30/2019] [Indexed: 12/26/2022] Open
Abstract
Many nutrients are absorbed via Na+ cotransport systems, and therefore it is predicted that nutrient absorption mechanisms require a large amount of luminal Na+. It is thought that Na+ diffuses back into the lumen via paracellular pathways to support Na+ cotransport absorption. However, direct experimental evidence in support of this mechanism has not been shown. To elucidate this, we took advantage of claudin-15 deficient (cldn15-/-) mice, which have been shown to have decreased paracellular Na+ permeability. We measured glucose-induced currents (ΔIsc) under open- and short-circuit conditions and simultaneously measured changes in unidirectional 22Na+ fluxes (ΔJNa) in Ussing chambers. Under short-circuit conditions, application of glucose resulted in an increase in ΔIsc and unidirectional mucosal to serosal 22Na+ (∆JNaMS) flux in both wild-type and cldn15-/- mice. However, under open-circuit conditions, ΔIsc was observed but ∆JNaMS was strongly inhibited in wild-type but not in cldn15-/- mice. In addition, in the duodenum of mice treated with cholera toxin, paracellular Na+ conductance was decreased and glucose-induced ∆JNaMS increment was observed under open-circuit conditions. We concluded that the Na+ which is absorbed by Na+-dependent glucose cotransport is recycled back into the lumen via paracellular Na+ conductance through claudin-15, which is driven by Na+ cotransport induced luminal negativity.
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Sollanek KJ, Kenefick RW, Cheuvront SN. Osmolality of Commercially Available Oral Rehydration Solutions: Impact of Brand, Storage Time, and Temperature. Nutrients 2019; 11:nu11071485. [PMID: 31261904 PMCID: PMC6682936 DOI: 10.3390/nu11071485] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 06/26/2019] [Accepted: 06/27/2019] [Indexed: 11/16/2022] Open
Abstract
Oral rehydration solutions (ORS) are specifically formulated with an osmolality to optimize fluid absorption. However, it is unclear how many ORS products comply with current World Health Organization (WHO) osmolality guidelines and the osmotic shelf-life stability is not known. Therefore, the purpose of this investigation was to examine the within and between ORS product osmolality variation in both pre-mixed and reconstituted powders. Additionally, the osmotic stability was examined over time. The osmolality of five different pre-mixed solutions and six powdered ORS products were measured. Pre-mixed solutions were stored at room temperatures and elevated temperatures (31 °C) for two months to examine osmotic shelf stability. Results demonstrated that only one pre-mixed ORS product was in compliance with the current guidelines both before and after the prolonged storage. Five of the six powdered ORS products were in compliance with minimal inter-packet variation observed within the given formulations. This investigation demonstrates that many commercially available pre-mixed ORS products do not currently adhere to the WHO recommended osmolality guidelines. Additionally, due to the presence of particular sugars and possibly other ingredients, the shelf-life stability of osmolality for certain ORS products may be questioned. These findings should be carefully considered in the design of future ORS products.
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Affiliation(s)
- Kurt J Sollanek
- Department of Kinesiology, Sonoma State University, Rohnert Park, CA 94928, USA.
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Bossi P, Antonuzzo A, Cherny NI, Rosengarten O, Pernot S, Trippa F, Schuler U, Snegovoy A, Jordan K, Ripamonti CI. Diarrhoea in adult cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2018; 29:iv126-iv142. [PMID: 29931177 DOI: 10.1093/annonc/mdy145] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- P Bossi
- Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
| | - A Antonuzzo
- U.O. Oncologia Medica 1, Polo Oncologico Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - N I Cherny
- Oncology Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - O Rosengarten
- Oncology Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - S Pernot
- Department of Hepato-Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, APHP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - F Trippa
- Radiation Oncology Centre, "S. Maria" Hospital, Terni, Italy
| | - U Schuler
- Department of Internal Medicine I, Palliative Care Centre, University Hospital Carl Gustav Carus, Dresden, Germany
| | - A Snegovoy
- N.N. Blokhin Russian Cancer Research Center, Moscow, Russia
| | - K Jordan
- Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany
| | - C I Ripamonti
- Oncology-Supportive Care in Cancer Unit, Department Onco-Haematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Guidelines for Burn Care Under Austere Conditions: Introduction to Burn Disaster, Airway and Ventilator Management, and Fluid Resuscitation. J Burn Care Res 2018; 37:e427-39. [PMID: 27224004 DOI: 10.1097/bcr.0000000000000304] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Cheuvront SN, Kenefick RW, Charkoudian N, Mitchell KM, Luippold AJ, Bradbury KE, Vidyasagar S. Efficacy of Glucose or Amino Acid-Based Commercial Beverages in Meeting Oral Rehydration Therapy Goals After Acute Hypertonic and Isotonic Dehydration. JPEN J Parenter Enteral Nutr 2018; 42:1185-1193. [DOI: 10.1002/jpen.1142] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Accepted: 11/30/2017] [Indexed: 01/04/2023]
Affiliation(s)
| | | | - Nisha Charkoudian
- U.S. Army Research Institute of Environmental Medicine; Natick MA USA
| | | | - Adam J. Luippold
- U.S. Army Research Institute of Environmental Medicine; Natick MA USA
| | | | - Sadasivan Vidyasagar
- Department of Radiation Oncology; University of Florida Health Cancer Center; Cancer and Genetics Research; Gainesville FL USA
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Abstract
Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases.
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Sarwar S, Ali A, Pal M, Chakrabarti P. Zinc oxide nanoparticles provide anti-cholera activity by disrupting the interaction of cholera toxin with the human GM1 receptor. J Biol Chem 2017; 292:18303-18311. [PMID: 28882894 PMCID: PMC5672052 DOI: 10.1074/jbc.m117.793240] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 09/04/2017] [Indexed: 11/06/2022] Open
Abstract
Vibrio cholerae causes cholera and is the leading cause of diarrhea in developing countries, highlighting the need for the development of new treatment strategies to combat this disease agent. While exploring the possibility of using zinc oxide (ZnO) nanoparticles (NPs) in cholera treatment, we previously found that ZnO NPs reduce fluid accumulation in mouse ileum induced by the cholera toxin (CT) protein. To uncover the mechanism of action of ZnO NPs on CT activity, here we used classical (O395) and El Tor (C6706) V. cholerae biotypes in growth and biochemical assays. We found that a ZnO NP concentration of 10 μg/ml did not affect the growth rates of these two strains, nor did we observe that ZnO NPs reduce the expression levels of CT mRNA and protein. It was observed that ZnO NPs form a complex with CT, appear to disrupt the CT secondary structure, and block its interaction with the GM1 ganglioside receptor in the outer leaflet of the plasma membrane in intestinal (HT-29) cells and thereby reduce CT uptake into the cells. In the range of 2.5-10 μg/ml, ZnO NPs exhibited no cytotoxicity on kidney (HEK293) and HT-29 cells. We conclude that ZnO NPs prevent the first step in the translocation of cholera toxin into intestinal epithelial cells without exerting measurable toxic effects on HEK293 and HT-29 cells.
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Affiliation(s)
| | - Asif Ali
- Division of Molecular Medicine, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata, India
| | - Mahadeb Pal
- Division of Molecular Medicine, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata, India
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Freedman SB, Tarr PI, Mahajan P. Re: Fruit Juice and Child Health. Pediatrics 2017; 140:peds.2017-2301A. [PMID: 28970341 DOI: 10.1542/peds.2017-2301a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Abstract
Intravenous (IV) cannulation and sterile IV salt solutions may not be options in resource-limited settings (RLSs). This article presents recipes for fluid resuscitation in the aftermath of burns occurring in RLSs. Burns of 20% total body surface area (TBSA) can be resuscitated, and burns up to 40% TBSA can most likely be resuscitated, using oral resuscitation solutions (ORSs) with salt supplementation. Without IV therapy, fluid resuscitation for larger burns may only be possible with ORSs. Published global experience is limited, and the magnitude of burn injuries that successfully respond to World Health Organization ORSs is not well-described.
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Affiliation(s)
- Michael Peck
- Arizona Burn Center, Maricopa Medical Center, 2601 East Roosevelt Street, Phoenix, AZ 85008, USA.
| | - James Jeng
- Mount Sinai Healthcare System, New York, NY, USA
| | - Amr Moghazy
- Suez Canal University, Suez Canal University Hospitals, Ismailia, Egypt
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Chisti MJ, Ahmed T, Ahmed AMS, Sarker SA, Faruque ASG, Islam MM, Huq S, Shahrin L, Bardhan PK, Salam MA. Hypernatremia in Children With Diarrhea: Presenting Features, Management, Outcome, and Risk Factors for Death. Clin Pediatr (Phila) 2016; 55:654-63. [PMID: 26810623 DOI: 10.1177/0009922815627346] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
We sought to investigate the magnitude, clinical features, treatment, and outcome of children suffering from hypernatremic diarrhea and to identify risk factors for fatal outcome among them. We reviewed 2 data sets of children <15 years admitted to the in-patient ward of the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b) with diarrhea and hypernatremia (serum sodium ≥150 mmol/L): (a) March 2001 to March 2002 (n = 371) and (b) March 2009 to August 2011 (n = 360). We reviewed their records and collected relevant information for analyses. The prevalence of hypernatremia was 5.1% (371/7212) and 2.4% (360/15 219), case fatality rate was 15% and 19%, respectively. In logistic regression analysis, the risk for death significantly increased in association with serum sodium ≥170 mmol/L, nutritional edema, hypoglycemia, respiratory distress, and absent peripheral pulses and reduced with the sole use of oral rehydration salts (ORS) or ORS following intravenous fluid, if indicated (for all, P < .05). Thus, managing children with hypernatremia using only ORS or ORS following intravenous fluid may help reduce the number of deaths.
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Affiliation(s)
- Mohammad Jobayer Chisti
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Tahmeed Ahmed
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - A M Shamshir Ahmed
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Shafiqul Alam Sarker
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Abu Syed Golam Faruque
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Md Munirul Islam
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Sayeeda Huq
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Lubaba Shahrin
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Pradip Kumar Bardhan
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
| | - Mohammed Abdus Salam
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
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Riddle MS, DuPont HL, Connor BA. ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults. Am J Gastroenterol 2016; 111:602-22. [PMID: 27068718 DOI: 10.1038/ajg.2016.126] [Citation(s) in RCA: 195] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 03/16/2016] [Indexed: 12/11/2022]
Abstract
Acute diarrheal infections are a common health problem globally and among both individuals in the United States and traveling to developing world countries. Multiple modalities including antibiotic and non-antibiotic therapies have been used to address these common infections. Information on treatment, prevention, diagnostics, and the consequences of acute diarrhea infection has emerged and helps to inform clinical management. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis, prevention, and treatment of acute diarrhea infection in both US-based and travel settings.
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Affiliation(s)
- Mark S Riddle
- Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland, USA
| | - Herbert L DuPont
- University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Bradley A Connor
- Weill Medical College of Cornell University, New York, New York, USA
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Abstract
An estimated 700 000 children die annually due to diarrhea with majority of these occurring in children under the age of 5 years. Morbidity from diarrhea includes poor growth and development. The global diarrhea burden is primarily due to infections secondary to rotavirus, cryptosporidium, enterotoxigenic Escherichia coli, and Shigella species. Known interventions to effectively treat and prevent diarrhea include vaccines against rotavirus and cholera, zinc supplementation, and therapy with oral rehydration solution. The achievement of the fourth Millennium Development Goal requires reductions in mortality from diarrhea, and can only be accomplished by implementing evidence-based strategies.
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Brandt KG, Antunes MMDC, da Silva GAP. Acute diarrhea: evidence‐based management. JORNAL DE PEDIATRIA (VERSÃO EM PORTUGUÊS) 2015. [DOI: 10.1016/j.jpedp.2015.09.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Brandt KG, Castro Antunes MMD, Silva GAPD. Acute diarrhea: evidence-based management. J Pediatr (Rio J) 2015; 91:S36-43. [PMID: 26351768 DOI: 10.1016/j.jped.2015.06.002] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 06/05/2015] [Accepted: 06/08/2015] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES To describe the current recommendations on the best management of pediatric patients with acute diarrheal disease. DATA SOURCE PubMed, Scopus, Google Scholar. DATA SUMMARY There has been little progress in the use of oral rehydration salts (ORS) in recent decades, despite being widely reported by international guidelines. Several studies have been performed to improve the effectiveness of ORS. Intravenous hydration with isotonic saline solution, quickly infused, should be given in cases of severe dehydration. Nutrition should be ensured after the dehydration resolution, and is essential for intestinal and immune health. Dietary restrictions are usually not beneficial and may be harmful. Symptomatic medications have limited indication and antibiotics are indicated in specific cases, such as cholera and moderate to severe shigellosis. CONCLUSIONS Hydration and nutrition are the interventions with the greatest impact on the course of acute diarrhea.
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Affiliation(s)
- Kátia Galeão Brandt
- Centro de Ciências da Saúde (CCS), Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil.
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Abstract
Diarrheal disease, which is most often caused by infectious pathogens, is a significant cause of morbidity and mortality worldwide, especially in children. This is particularly true in developing countries. Recent outbreaks of infectious diarrhea in developed countries, including the USA, are often attributed to food handling and distribution practices and highlight the need for continued vigilance in this area. Another common cause of infectious diarrhea, Clostridium difficile infection (CDI), has historically been associated with the use of antibiotics and exposure to a health-care setting but is now increasingly common in the community in persons who lack the typical risk factors. Recent scientific advances have also led to new and proposed new therapies for infectious diarrhea, including fecal microbiota transplant (FMT) for recurrent C. difficile infection (RCDI), probiotics for prevention of antibiotic-associated diarrhea (AAD) and CDI, and the use of zinc supplementation in the treatment of acute diarrhea in children. Other therapies that have been in use for decades, such as the oral rehydration solution (ORS), continue to be the targets of scientific advancement in an effort to improve delivery and efficacy. Finally, post-infectious irritable bowel syndrome (PI-IBS) is an increasingly recognized occurrence. Attempts to understand the mechanism behind this phenomenon are underway and may provide insight into potential treatment options.
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Affiliation(s)
- Brandon Dickinson
- Department of Medicine, University of Washington School of Medicine, Seattle, USA
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Evaluation of the role of zinc supplementation in treatment of diarrhoea in paediatric patients: a randomized open-label study. DRUGS & THERAPY PERSPECTIVES 2015. [DOI: 10.1007/s40267-014-0169-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Binder HJ, Brown I, Ramakrishna BS, Young GP. Oral rehydration therapy in the second decade of the twenty-first century. Curr Gastroenterol Rep 2014; 16:376. [PMID: 24562469 PMCID: PMC3950600 DOI: 10.1007/s11894-014-0376-2] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Oral rehydration solution (ORS) was established as the cornerstone of therapy for dehydration secondary to acute infectious diarrhea approximately 40 years ago. The efficacy of ORS is based on the ability of glucose to stimulate Na and fluid absorption in the small intestine via a cyclic AMP-independent process. Despite the establishment that ORS is the primary reason for the substantial reduction in morbidity and mortality from diarrhea in children in developing countries, the use of ORS has lagged for many reasons. This review highlights efforts to establish a major reformulation of ORS following the demonstration that short-chain fatty acids (SCFA) stimulate colonic Na and fluid absorption by a cyclic AMP-independent mechanism. The addition of high-amylose maize starch (HAMS), a microbially-fermentable (or 'resistant') starch, to ORS results in delivery of non-absorbed carbohydrate to the colon where it is fermented to SCFA. To date, three randomized controlled trials with a HAMS-ORS in south India have demonstrated a substantial decrease in diarrhea duration in both adults and children hospitalized for acute diarrhea. Significant efforts are now underway to establish this dual-action, modified HAMS-hypoosmolar ORS solution as the standard ORS for the treatment of dehydration from acute diarrhea.
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Affiliation(s)
- Henry J. Binder
- Department of Internal Medicine, Yale School of Medicine, P.O. Box 208019, New Haven, CT 06520 USA
| | - Ian Brown
- Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, SA Australia
| | - B. S. Ramakrishna
- SRM Institutes for Medical Sciences, Vadapalani, Chennai, 600 026 India
| | - Graeme P. Young
- Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, SA Australia
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Preoperative oral rehydration therapy with 2.5 % carbohydrate beverage alleviates insulin action in volunteers. J Artif Organs 2013; 16:483-8. [PMID: 23917335 DOI: 10.1007/s10047-013-0722-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Accepted: 07/22/2013] [Indexed: 02/05/2023]
Abstract
Preoperative carbohydrate loading enhances insulin action by approximately 50 %. In some Japanese hospitals, preoperative oral rehydration therapy is performed for preventing dehydration during surgery. We hypothesized that preoperative oral rehydration therapy with a 2.5 % carbohydrate beverage that is widely used in Japan can enhance insulin action. Therefore, we investigated the effect of this 2.5 % carbohydrate beverage on insulin action in volunteers. Six healthy volunteers participated in this crossover randomized study. The participants were segregated into 2 groups: an oral rehydration therapy with 2.5 % carbohydrate beverage group (group A) and a control group (group B). Subjects in group B were allowed to drink only water from 9 pm the day before the test; conversely, group A fasted from 9 pm onward and drank 500 ml of the beverage containing 2.5 % carbohydrate (OS-1; Otsuka Pharmaceutical Factory, Tokushima, Japan) between 9 and 12 pm and again at 6.30 am. At 8.30 am, a hyperinsulinemic normoglycemic clamp was initiated using an artificial pancreas STG-22 (Nikkiso, Tokyo, Japan). Insulin action was evaluated in both groups using the glucose infusion rate. Blood glucose levels at the initiation of the clamp procedure were similar. However, the glucose infusion rate for group A was significantly higher than that of group B (8.6 ± 1.5 vs. 6.8 ± 2.0 mg/kg/min, p = 0.009). In conclusion, the hyperinsulinemic normoglycemic clamp using an artificial pancreas showed that the administration of a 2.5 % carbohydrate oral rehydration solution for preoperative oral rehydration therapy improves insulin action in volunteers.
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Grünberg W, Hartmann H, Arlt S, Burfeind O, Staufenbiel R. Alkalinizing effect of NaHCO₃ with and without glucose when administered orally to euhydrated neonatal dairy calves. J Dairy Sci 2013; 96:3895-906. [PMID: 23548282 DOI: 10.3168/jds.2012-6202] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Accepted: 02/12/2013] [Indexed: 01/27/2023]
Abstract
The use of oral rehydration solutions (ORS) is well established as an effective treatment to correct water-, electrolyte-, and acid-base balance in diarrheic calves. The main ingredients of a commercial ORS are Na, glucose, and alkalinizing agents, such as NaHCO3. Particular importance is attributed to the combination of glucose and Na at a specific ratio to optimize intestinal sodium, and thereby water uptake, through the sodium-glucose co-transport. Enhancing intestinal Na absorption by combining glucose and Na in an ORS has the potential to improve the alkalinizing effect of an ORS according the strong ion theory. The objective of this study was to investigate the effect of glucose on the alkalinizing effect of NaHCO3 when administered orally. Nine healthy neonatal Holstein-Friesian calves underwent 3 oral treatments with 2-L solutions of NaHCO3 (150 mmol/L), glucose (300 mmol/L), and glucose + NaHCO3 (300 mmol/L + 150 mmol/L, respectively) in randomized order. Arterial and venous blood was obtained before treatment and in 30-min intervals thereafter for blood gas analysis and determination of plasma protein and electrolyte concentrations. Urine was collected volumetrically to determine urine volume, osmolality, pH, net acid excretion, and renal Na excretion after treatment. Plasma volume changes were extrapolated from plasma protein concentration changes. Treatment and time effects were tested with repeated measures ANOVA. Only subtle differences between oral administration of NaHCO3, with and without glucose, were observed for the change of the standard HCO3 concentration relative to baseline. No differences in plasma Na, plasma volume expansion, renal Na, net base excretion, urine volume, or pH could be identified between animals treated orally with NaHCO3 with and without glucose. Similarly, no differences in blood glucose concentration, plasma volume expansion, urine volume, or renal glucose excretion were observed in the 8h after treatment when comparing oral glucose treatment with and without NaHCO3. Our results indicate that combination of NaHCO3 with glucose in a hypertonic ORS only had a minor effect on the alkalinizing effect of NaHCO3, which is unlikely to be of clinical relevance. The combination of NaHCO3 and glucose neither improved Na, glucose, nor water absorption in euhydrated neonatal dairy calves, questioning the relevance of a specific ratio between Na and glucose in ORS for calves.
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Affiliation(s)
- W Grünberg
- Department of Farm Animal Health, Universiteit Utrecht, Utrecht, The Netherlands.
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Musekiwa A, Volmink J. Oral rehydration salt solution for treating cholera: ≤ 270 mOsm/L solutions vs ≥ 310 mOsm/L solutions. Cochrane Database Syst Rev 2011; 2011:CD003754. [PMID: 22161381 PMCID: PMC6532622 DOI: 10.1002/14651858.cd003754.pub3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Oral rehydration solution (ORS) is used to treat the dehydration caused by diarrhoeal diseases, including cholera. ORS formulations with an osmolarity (a measure of solute concentration) of ≤ 270 mOsm/L (ORS ≤ 270) are safe and more effective than ORS formulations with an osmolarity of ≥ 310 mOsm/L (ORS ≥ 310) for treating non-cholera diarrhoea. As cholera causes rapid electrolyte loss, it is important to know if these benefits are similar for people suffering from cholera. OBJECTIVES To compare the safety and efficacy of ORS ≤270 with ORS ≥ 310 for treating dehydration due to cholera. SEARCH METHODS We searched the Cochrane Infectious Disease Group Specialized Register (April 2011), CENTRAL (The Cochrane Library Issue 4, 2011), MEDLINE (1966 to April 2011), EMBASE (1974 to April 2011), and LILACS (1982 to April 2011). We also contacted organizations and searched reference lists. SELECTION CRITERIA Randomized controlled trials comparing ORS ≤ 270 with ORS ≥ 310 for treating adults and children with acute diarrhoea due to cholera. DATA COLLECTION AND ANALYSIS Two reviewers independently applied eligibility criteria, assessed trial quality, and extracted data. We pooled dichotomous data using risk ratio (RR), pooled continuous data using mean difference (MD) or the standardized mean difference (SMD), and presented the results with 95% confidence intervals (CI). MAIN RESULTS For glucose-based ORS, seven trials (718 participants) met the inclusion criteria. Biochemical hyponatraemia (blood sodium levels < 130 mmol/L) was more common with ORS ≤ 270 (RR 1.67, CI 1.09 to 2.57; 465 participants, four trials), while a higher level of severe biochemical hyponatraemia (blood sodium levels < 125 mmol/L) in the same group was not significant (RR 1.58, CI 0.62 to 4.04; 465 participants, four trials). No instances of symptomatic hyponatraemia or death were noted in the trials that intended to record them. We found no statistically significant difference in the need for unscheduled intravenous infusion. Analyses separating children and adults showed no obvious trends.Two trials also examined rice-based ORS. In the ORS ≤ 270 group, duration of diarrhoea was shorter (MD -11.42 hours, CI -13.80 to -9.04; 102 participants, two trials). AUTHORS' CONCLUSIONS In people with cholera, ORS ≤ 270 is associated with biochemical hyponatraemia when compared with ORS ≥ 310, but there are no differences in terms of other outcomes. Although this risk does not appear to be associated with any serious consequences, the total patient experience in existing trials is small. Under wider practice conditions, especially where patient monitoring is difficult, caution is warranted.
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Affiliation(s)
- Alfred Musekiwa
- University of the WitwatersrandWits Reproductive Health & HIV Institute (WRHI), Faculty of Health SciencesPO Box 18512HillbrowJohannesburgSouth Africa2038
- South African Cochrane Centre, Medical Research Council of South AfricaCape TownSouth Africa
| | - Jimmy Volmink
- Stellenbosch UniversityFaculty of Health SciencesPO Box 19063TygerbergSouth Africa7505
- Medical Research Council of South AfricaSouth African Cochrane CentreCape TownSouth Africa
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Telmesani AM. Oral rehydration salts, zinc supplement and rota virus vaccine in the management of childhood acute diarrhea. J Family Community Med 2011; 17:79-82. [PMID: 21359029 PMCID: PMC3045093 DOI: 10.4103/1319-1683.71988] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Acute diarrhea remains a major cause of morbidity and mortality in children. Since the introduction of oral rehydration salts (ORS) mortality has dropped to less than 50% worldwide. Low osmolarity ORS improved the outcome and reduced the hospitalization further. Zinc difficiency has been found to be associated with severe episodes of acute diarrhea. Zinc supplement in developing countries did reduce the incidence and prevalence of diarrhea. In addition, Zinc supplement significantly reduced the severity of diarrhea and duration of the episode. In the Americas and Europe, Rota virus vaccine was 90% effective in preventing severe episodes of severe rotavirus gastroenteritis. This review concludes that low osmolarilty ORS, zinc supplementation and rotavirus vaccine are major factors in reducing the morbidity, mortality and hospitalization resulting from to acute gastroenteritis in childhood.
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Affiliation(s)
- Abdulwahab Ma Telmesani
- Department of Pediatrics, College of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia
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Suh JS, Hahn WH, Cho BS. Recent Advances of Oral Rehydration Therapy (ORT). Electrolyte Blood Press 2010; 8:82-6. [PMID: 21468201 PMCID: PMC3043760 DOI: 10.5049/ebp.2010.8.2.82] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Accepted: 11/24/2010] [Indexed: 12/14/2022] Open
Abstract
Diarrheal disease is one of the leading causes of worldwide morbidity and mortality, especially in children. It causes loss of body fluid, which may lead to severe dehydration, electrolyte imbalance, shock and even to death. The mortality rate from acute diarrhea has decreased over the last few decades. This decline, especially in developing countries is largely due to the implantation of the standard World Health Organization-oral rehydration solution (WHO-ORS). However, the use of standard ORS has been limited by its inability to reduce fecal volume or diarrhea duration. Subsequently, this has led to various attempts to modify its compositions. And these modifications include the use of reduced osmolarity ORS, polymer-based ORS and zinc supplementation. Some of these variations have been successful and others are still under investigation. Therefore, further trials are needed to progress toward the ideal ORS. In this article, we briefly reviewed the pathophysiologic basis of the ORS, followed by the standard WHO-ORS and several modifications to improve the ORS.
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Affiliation(s)
- Jin-Soon Suh
- Department of Pediatrics, East West Kidney Disease Institute, School of Medicine, Kyung Hee University, Seoul, Korea
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Abstract
Epithelia form barriers that are essential to life. This is particularly true in the intestine, where the epithelial barrier supports nutrient and water transport while preventing microbial contamination of the interstitial tissues. Along with plasma membranes, the intercellular tight junction is the primary cellular determinant of epithelial barrier function. Disruption of tight junction structure, as a result of specific protein mutations or aberrant regulatory signals, can be both a cause and an effect of disease. Recent advances have provided new insights into the extracellular signals and intracellular mediators of tight junction regulation in disease states as well as into the interactions of intestinal barrier function with mucosal immune cells and luminal microbiota. In this review, we discuss the critical roles of the tight junction in health and explore the contributions of barrier dysfunction to disease pathogenesis.
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Affiliation(s)
- Amanda M Marchiando
- Department of Pathology, Graduate Program in Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, Illinois, 60637, USA.
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A randomized controlled trial of glucose versus amylase resistant starch hypo-osmolar oral rehydration solution for adult acute dehydrating diarrhea. PLoS One 2008; 3:e1587. [PMID: 18270575 PMCID: PMC2217593 DOI: 10.1371/journal.pone.0001587] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2007] [Accepted: 01/16/2008] [Indexed: 11/30/2022] Open
Abstract
Background Reduction of gross diarrhea rate in excess of that seen over time with intravenous therapy and appropriate antibiotics is not usually achieved by oral glucose-electrolyte rehydration therapy for cholera and cholera-like diarrheas. Methodology and Principal Findings This prospective randomized clinical trial at a tertiary referral hospital in southern India was undertaken to determine whether amylase resistant starch, substituting for glucose in hypo-osmolar oral rehydration solution, would reduce diarrhea duration and weight in adults with acute severe dehydrating diarrhea. 50 adult males with severe watery diarrhea of less than three days' duration and moderate to severe dehydration were randomized to receive hypo-osmolar ORS (HO-ORS) or HO-ORS in which amylase resistant high amylose maize starch 50g/L substituted for glucose (HAMS-ORS). All remaining therapy followed standard protocol. Duration of diarrhea (ORS commencement to first formed stool) in hours was significantly shorter with HAMS-ORS (median 19, IQR 10-28) compared to HO-ORS (median 42, IQR 24-50) (Bonferroni adjusted P, Padj<0.001). Survival analysis (Kaplan-Meier) showed faster recovery from diarrhea in the HAMS-ORS group (P<0.001, log rank test). Total diarrhea fecal weight in grams (median, IQR) was not significantly lower in the HAMS-ORS group (2190, 1160-5635) compared to HO-ORS (5210, 2095-12190) (Padj = 0.08). However, stool weight at 13-24 hours (280, 0-965 vs. 1360, 405-2985) and 25–48 hours (0, 0-360 vs. 1080, 55-3485) were significantly lower in HAMS-ORS compared to HO-ORS group (Padj = 0.048 and P = 0.012, respectively). ORS intake after first 24 hours was lower in the HAMS-ORS group. Subgroup analysis of patients with culture isolates of Vibrio cholerae indicated similar significant differences between the treatment groups. Conclusions Compared to HO-ORS, HAMS-ORS reduced diarrhea duration by 55% and significantly reduced fecal weight after the first 12 hours of ORS therapy in adults with cholera-like diarrhea. Trial Registration Current Controlled Trials ISRCTN72841333
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Affiliation(s)
- Adam J Moeser
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA
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Subramanya S, Ramakrishna BS, Binder HJ, Farthing MJ, Young GP. Evaluation of oral rehydration solution by whole-gut perfusion in rats: effect of osmolarity, sodium concentration and resistant starch. J Pediatr Gastroenterol Nutr 2006; 43:568-75. [PMID: 17130730 DOI: 10.1097/01.mpg.0000239998.43141.b2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Reduced osmolarity oral rehydration solution (ORS) improved small bowel absorption of fluid and electrolytes in segmental perfusion in experimental animals; this was borne out in clinical practice. Adding amylase-resistant starch (RS) to ORS is expected to increase colonic fluid absorption. This study used combined small and large bowel perfusion to evaluate combinations of reduced osmolarity and starch in ORS. METHODS Single-pass steady-state perfusions of the whole gut at 30 mL/h, using the nonabsorbable marker C-polyethylene glycol 4000, were performed in Wistar rats after exposure to cholera toxin or Escherichia coli heat-stable enterotoxin (STa). RESULTS Steady state was established within 90 minutes after commencing perfusion. Net secretion of water, sodium and chloride induced by cholera toxin was partially reversed by standard glucose-ORS (G-ORS). Substituting glucose in G-ORS with RS (RS-ORS) substantially increased net water absorption (P < 0.001) as did reduced osmolarity ORS (RO-ORS) (P < 0.001); addition of RS to RO-ORS further increased water absorption (P < 0.001). In STa-treated intestine, RO-ORS and RS-ORS significantly improved water absorption compared to G-ORS (P < 0.005). RO- and RS-RO-ORS did not significantly augment net electrolyte absorption compared with G-ORS. RS-ORS was associated with highest net absorption of sodium and chloride compared with all other groups. CONCLUSIONS RS increased net water (and sodium) absorption from isosmolar and reduced osmolar ORS consistent with increased absorption by the colon. RS in reduced osmolar ORS may have advantages to reduce severity of diarrhea and prevent hyponatremia in severe diarrhea and may be applicable to diarrhea of different etiologies.
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Affiliation(s)
- Sandeep Subramanya
- Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
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Cancio LC, Kramer GC, Hoskins SL. Gastrointestinal Fluid Resuscitation of Thermally Injured Patients. J Burn Care Res 2006; 27:561-9. [PMID: 16998386 DOI: 10.1097/01.bcr.0000235449.05828.b8] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Leopoldo C Cancio
- U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas 78234-6315, USA
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Hu Z, Wang Y, Graham WV, Su L, Musch MW, Turner JR. MAPKAPK-2 is a critical signaling intermediate in NHE3 activation following Na+-glucose cotransport. J Biol Chem 2006; 281:24247-53. [PMID: 16793766 DOI: 10.1074/jbc.m602898200] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Villus enterocyte nutrient absorption occurs via precisely orchestrated interactions among multiple transporters. For example, transport by the apical Na(+)-glucose cotransporter, SGLT1, triggers translocation of NHE3, Na(+)-H(+) antiporter isoform 3, to the plasma membrane. This translocation requires activation of p38 mitogen-activated protein kinase (MAPK), Akt2, and ezrin. Akt2 directly phosphorylates ezrin, but the precise role of p38 MAPK in this process remains to be defined. Sequence analysis suggested that p38 MAPK could not directly phosphorylate Akt2. We hypothesized that MAPKAPK-2 might link p38 MAPK and Akt2 activation. MAPKAPK-2 was phosphorylated after initiation of Na(+)-glucose cotransport with kinetics that paralleled activation of p38 MAPK, Akt2, and ezrin. MAPKAPK-2, Akt2, and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression. Akt2 inhibition blocked ezrin but not p38 MAPK or MAPKAPK-2 phosphorylation, suggesting that MAPKAPK-2 could be an intermediate in p38 MAPK-dependent Akt2 activation. Consistent with this, MAP-KAPK-2 could phosphorylate an Akt2-derived peptide in vitro. siRNA-mediated MAPKAPK-2 knockdown inhibited phosphorylation of Akt2 and ezrin but not p38 MAPK. MAPKAPK-2 knockdown also blocked NHE3 translocation. Thus, MAP-KAPK-2 controls Akt2 phosphorylation. In so doing, MAP-KAPK-2 links p38 MAPK to Akt2, ezrin, and NHE3 activation after SGLT1-mediated transport.
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Affiliation(s)
- Zhihong Hu
- Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA
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Hoque KM, Binder HJ. Zinc in the treatment of acute diarrhea: current status and assessment. Gastroenterology 2006; 130:2201-5. [PMID: 16762641 DOI: 10.1053/j.gastro.2006.02.062] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2005] [Accepted: 02/15/2006] [Indexed: 12/02/2022]
Abstract
The improved treatment of acute diarrhea in children during the past 35 years has reduced its morbidity and mortality substantially. However, better therapy still is required. This article reviews the role of oral rehydration solution in the treatment of acute diarrhea with particular attention to recent efforts to develop improved oral rehydration solution formulations. One promising approach is the administration of Zinc (Zn). Based on its beneficial effects in infections, including pneumonia, Zn has been shown to be effective in the treatment of acute diarrhea in several randomized controlled trials including subsequent meta-analyses. Thus, an emerging body of clinical data indicates that Zn can be useful for treating acute diarrhea. However, only limited information is known about the mechanism(s) by which Zn reduces diarrhea. Recent studies have indicated that Zn acts as a K channel blocker of adenosine 3',5'-cyclic monophosphate-mediated chlorine secretion, but may not affect either Ca2+- or guanosine 3',5'-cyclic monophosphate-mediated chlorine secretion. These data provide a strong rationale for further trials testing its efficacy in specific clinical settings and for more detailed physiologic studies examining how Zn exerts its antidiarrheal effect.
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Affiliation(s)
- Kazi Mirajul Hoque
- Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
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Raghupathy P, Ramakrishna BS, Oommen SP, Ahmed MS, Priyaa G, Dziura J, Young GP, Binder HJ. Amylase-resistant starch as adjunct to oral rehydration therapy in children with diarrhea. J Pediatr Gastroenterol Nutr 2006; 42:362-8. [PMID: 16641573 DOI: 10.1097/01.mpg.0000214163.83316.41] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Oral rehydration solution (ORS) for treatment of diarrhea relies on enhancement of small intestinal sodium and fluid absorption to correct dehydration. Amylase-resistant starch added to ORS significantly reduced the duration and severity of diarrhea in adults with cholera, presumably by generation of short-chain fatty acids in the colon and enhancement of colonic sodium and fluid absorption. The present study was initiated to determine whether addition of amylase-resistant starch to standard World Health Organization glucose-ORS (G-ORS) would reduce the duration of diarrhea and fecal fluid losses in children with acute diarrhea. METHODS One hundred eighty-three children (6 months to 3 years) with acute watery diarrhea were randomized to receive either standard treatment with G-ORS or G-ORS with additional amylase-resistant starch, HAMS (HAMS-ORS, 50g/L). Stool weight and consistency were monitored serially until development of formed stool or development of treatment failure defined as either the need for unscheduled intravenous fluid therapy or diarrhea longer than 72 hours. RESULTS Five of the subjects were lost to follow up. In 178 remaining children (87 HAMS-ORS and 91 G-ORS) with evaluable data, time from enrolment to last unformed stool was significantly less in children receiving HAMS-ORS (median, 6.75 hours; 95% confidence interval, 4.27-9.22) than in children treated with G-ORS (12.80 hours, 8.69-16.91) (P = 0.0292). Time to first formed stool was also significantly shorter in children receiving HAMS-ORS (median, 18.25 hours; 95% confidence interval, 13.09-23.41) compared with children receiving G-ORS (median, 21.50 hours; 95% confidence interval, 17.26-25.74) (P = 0.0440). The total amount of ORS consumed was similar in both groups. There was a trend toward lower mean stool weight in first 24 hours (P = 0.0752) as well as total diarrheal stool weight (P = 0.0926) in patients in the HAMS group compared with the G-ORS group. CONCLUSION In children with acute diarrhea, the addition of amylase-resistant starch to glucose ORS significantly shortened duration of diarrhea compared with standard treatment.
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Affiliation(s)
- P Raghupathy
- Department of Child Health, Christian Medical College, Vellore, India
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Abstract
Diarrhea from gastrointestinal infection remains a common problem. In industrialized countries, management is aimed at reducing morbidity and defining groups that may benefit from further investigation. Most infectious diarrhea is self-limiting and only requires supportive management. Viral agents are increasingly recognized as causative agents of epidemic and sporadic diarrhea. In developing countries, diarrhea is a major cause of mortality in children. Oral rehydration therapy, guided by a clinical assessment of the degree of dehydration, is cheap, simple, and effective and remains the mainstay of management of infant diarrhea. Controversies focus on the optimal formulation of oral rehydration solution. A vaccine against rotavirus has the potential to save millions of lives worldwide.
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Affiliation(s)
- Allen C Cheng
- Menzies School of Health Research, Charles Darwin University, Darwin, Australia
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Goodman BE, Percy WH. CFTR in cystic fibrosis and cholera: from membrane transport to clinical practice. ADVANCES IN PHYSIOLOGY EDUCATION 2005; 29:75-82. [PMID: 15905150 DOI: 10.1152/advan.00035.2004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
We have used a brief analysis of transport via cystic fibrosis (CF) transmembrane conductance regulators (CFTRs) in various organ systems to highlight the importance of basic membrane transport processes across epithelial cells for first-year medical students in physiology. Because CFTRs are involved in transport both physiologically and pathologically in various systems, we have used this clinical correlation to analyze how a defective gene leading to defective transport proteins can be directly involved in the symptoms of cholera and CF. This article is a "Staying Current" approach to transport via CFTRs including numerous helpful references with further information for a teaching faculty member. The article follows our normal presentation which begins with a discussion of the involvement of CFTR transport in the intestine and how cholera affects intestinal transport, extends to CFTR transport in various organ systems in CF, and concludes with the logic behind many of the treatments that improve CF. Student learning objectives are included to assist in assessment of student understanding of the basic concepts.
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Affiliation(s)
- Barbara E Goodman
- Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, South Dakota 57069, USA.
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Abstract
BACKGROUND Oral rehydration solution (ORS) is used to treat dehydration caused by diarrheal diseases including cholera. Reduced osmolarity formulations are safe and more effective than standard ORS for treating non-cholera diarrhea. As cholera causes rapid electrolyte loss, it is important to know if these benefits are similar for people with cholera. OBJECTIVES To compare the safety and efficacy of reduced osmolarity oral rehydration solution (ORS) with standard ORS for treating diarrhea due to cholera. SEARCH STRATEGY We searched the Cochrane Infectious Disease Group Specialized Register (January 2004), CENTRAL (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1974 to January 2004), and LILACS (1982 to January 2004). We also contacted organizations and searched reference lists. SELECTION CRITERIA Randomized controlled trials comparing reduced osmolarity ORS with standard ORS for treating adults and children with acute diarrhea due to cholera. DATA COLLECTION AND ANALYSIS Two reviewers independently applied eligibility criteria, assessed trial quality, and extracted data. We pooled binary data using relative risks (RR), continuous data using weighted mean difference (WMD) or the standardized mean difference (SMD), and presented the results with 95% confidence intervals (CI). MAIN RESULTS For glucose-based reduced osmolarity ORS, seven trials (718 participants) met the inclusion criteria. Biochemical hyponatremia (serum sodium < 130 mmol/L) was more common with reduced osmolarity ORS (RR 1.67, CI 1.09 to 2.57; 465 participants, 4 trials); for severe biochemical hyponatremia (serum sodium < 125 mmol/L) this was not significant (RR 1.58, CI 0.62 to 4.04; 465 participants, 4 trials). No trials reported symptomatic hyponatremia or death. We found no statistically significant difference in the need for unscheduled intravenous infusion. Analyses separating children and adults showed no obvious trends. Two trials also examined rice-based ORS. In the reduced osmolarity group, duration of diarrhea was shorter (WMD -16.85 hours, CI -21.22 to -12.48; 102 participants, 2 trials). REVIEWERS' CONCLUSIONS In people with cholera, reduced osmolarity ORS is associated with biochemical hyponatremia when compared with standard ORS, although there are similar benefits in terms of other outcomes. Although this risk does not appear to be accompanied by serious consequences, the total patient experience in existing trials is small. Under wider practice conditions, especially where patient monitoring is difficult, caution is warranted.
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Affiliation(s)
- C Murphy
- Research and Analysis Department, Global Health Council, 1701 K Street, NW, Suite 600, Washington, DC 20006, USA.
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